Jara A, Chacón C, Valdivieso A, Aris L, Jalil R, Felsenfeld A J
Department of Nephrology, Hospital Clinico, Pontificia Universidad Catolica de Chile, Marcoleta 345, Santiago, Chile.
Nephrol Dial Transplant. 2001 May;16(5):1009-16. doi: 10.1093/ndt/16.5.1009.
Calcitriol is used to treat secondary hyperparathyroidism in dialysis patients. For similarly elevated parathyroid hormone (PTH) levels, the PTH response to calcitriol treatment is believed to be better in hypocalcaemic dialysis patients than in dialysis patients with higher serum calcium values. Furthermore, few studies have evaluated the rapidity of the rebound in serum PTH values after prolonged treatment with calcitriol. Our goal was to evaluate (i) the PTH response to calcitriol treatment in hypocalcaemic haemodialysis patients, (ii) the rapidity of rebound in PTH after calcitriol treatment was stopped, and (iii) whether the effect of calcitriol treatment on PTH levels could be separated from those produced by changes in serum calcium and phosphate values.
Eight haemodialysis patients (29+/-3 years) with hypocalcaemia and hyperparathyroidism were treated thrice weekly with 2 microg of intravenous calcitriol and were dialysed with a 3.5 mEq/l calcium dialysate. Parathyroid function (PTH-calcium curve) was determined before and after 30 weeks of calcitriol treatment and 15 weeks after calcitriol treatment was stopped.
Pretreatment PTH and ionized calcium values were 907+/-127 pg/ml and 3.89+/-0.12 mg/dl (normal, 4.52+/-0.07 mg/dl). During calcitriol treatment, one patient did not respond, but basal (predialysis) PTH values in the other seven patients decreased from 846+/-129 to 72+/-12 pg/ml, P<0.001 and in all seven patients, the decrease exceeded 85%. During the 15 weeks after calcitriol treatment was stopped, a slow rebound in basal PTH values in the seven patients was observed, 72+/-12 to 375+/-44 pg/ml. Covariance analysis was used to evaluate the three tests of parathyroid function (0, 30, and 45 weeks), and showed that calcitriol treatment was associated with reductions in maximal PTH values while reductions in basal PTH were affected by ionized calcium and serum phosphate. The basal/maximal PTH ratio and the set point of calcium were associated with changes in ionized calcium.
In haemodialysis patients with hypocalcaemia, (i) moderate to severe hyperparathyroidism responded well to treatment with calcitriol, (ii) reductions in maximal PTH were calcitriol dependent while reductions in basal PTH were affected by the ionized calcium and serum phosphate concentrations, (iii) changes in the basal/maximal PTH ratio and the set point of calcium were calcium dependent, and (iv) the delayed rebound in basal PTH levels after withdrawal of calcitriol treatment may have been due to the long duration of treatment and the marked PTH suppression during treatment.
骨化三醇用于治疗透析患者的继发性甲状旁腺功能亢进。对于甲状旁腺激素（PTH）水平同样升高的情况，人们认为低钙血症透析患者对骨化三醇治疗的PTH反应比血清钙值较高的透析患者更好。此外，很少有研究评估骨化三醇长期治疗后血清PTH值反弹的速度。我们的目标是评估：（i）低钙血症血液透析患者对骨化三醇治疗的PTH反应；（ii）骨化三醇治疗停止后PTH反弹的速度；（iii）骨化三醇治疗对PTH水平的影响是否能与血清钙和磷值变化所产生的影响区分开来。
8例患有低钙血症和甲状旁腺功能亢进的血液透析患者（29±3岁），每周静脉注射2μg骨化三醇三次，并使用钙浓度为3.5mEq/L的透析液进行透析。在骨化三醇治疗30周前后以及治疗停止15周后测定甲状旁腺功能（PTH-钙曲线）。
治疗前PTH和离子钙值分别为907±127pg/ml和3.89±0.12mg/dl（正常范围为4.52±0.07mg/dl）。在骨化三醇治疗期间，1例患者无反应，但其他7例患者的基础（透析前）PTH值从846±129pg/ml降至72±12pg/ml，P<0.001，且所有7例患者的下降幅度均超过85%。在骨化三醇治疗停止后的15周内，观察到这7例患者的基础PTH值缓慢反弹，从72±12pg/ml升至375±44pg/ml。采用协方差分析评估甲状旁腺功能的三项检测（0、30和45周），结果显示骨化三醇治疗与最大PTH值降低有关，而基础PTH降低受离子钙和血清磷影响。基础/最大PTH比值和钙设定点与离子钙变化有关。
在低钙血症的血液透析患者中，（i）中度至重度甲状旁腺功能亢进对骨化三醇治疗反应良好；（ii）最大PTH降低依赖于骨化三醇，而基础PTH降低受离子钙和血清磷浓度影响；（iii）基础/最大PTH比值和钙设定点的变化依赖于钙；（iv）骨化三醇治疗停止后基础PTH水平延迟反弹可能是由于治疗时间长以及治疗期间PTH受到显著抑制。
